Support is requested for a Keystone Symposia meeting entitled PI 3-Kinase Signaling Pathways in Disease, organized by Lori Friedman, David A. Fruman and Phillip T. Hawkins. The meeting will be held in Vancouver, British Columbia, Canada from January 13-18, 2015. The PI3K-Akt-mTOR signaling pathway is one of the primary mechanisms for controlling cell growth, survival, and motility in response to intracellular signaling and extracellular cues. Genetic events resulting in inappropriate activation of this pathway are common in many cancers and, as a result, are a focus of both basic cancer research and drug discovery efforts in oncology. The PI3K-Akt-mTOR network also controls diverse aspects of inflammation and adaptive immunity. Although originally modeled as an independent and linear signaling cascade, today it is evident that the PI3K pathway also functions as a central hub for cross-talk in both vertical as well as reciprocal feedback regulatio with other important signaling pathways. How metabolic pathways are regulated to meet the unique needs of tumor cells and activated lymphocytes is a fertile area of study, with mounting evidence that metabolic regulation is intimately linked with the signal transduction pathways that control cell growth and proliferation. One of the exciting advances in the field is the development of new inhibitors against this pathway. However, the rationale for inhibiting individual or multipl isoforms of PI3K/Akt/mTOR signaling remains a subject of intense debate. This Keystone Symposia meeting aims to bring together scientists and clinicians from academia and industry to discuss the opportunities and liabilities of targeting the PI3K- and related pathways in disease, drawing on human pathophysiology and genetics, preclinical models and clinical data with PI3K pathway inhibitors. A joint meeting on Integrating Metabolism and Tumor Biology will enhance opportunities for interdisciplinary interactions. In addition, the integration of attendees from both meetings will help increase our understanding of the PI3K pathway in the context of cancer, thereby improving outcomes for cancer patients.